The mesangium of the renal glomerulus is capable of taking up immune complex-like materials from their initial sites of localization in the subendothelial space of the glomerular capillary wall. This mesangial transport system is thus a putative important determinant of the histologic pattern and nephritogenicity of immune complex localization in the glomerulus. This proposal will capitalize upon a system developed for quantitation of mesangial uptake and subsequent efferent clearance of immunoglobulin aggregates as analogues of immune complexes. In particular, the influence of the immunoglobulin subclass of aggregates on their intraglomerular handling by the mesangial system and on their localization and kinetics in other tissues will be determined in detail. A complementary study will pursue the development of a mouse model of the form of human glomerulonephritis called mesangial IgA nephropathy. This will be induced by intragastric immunization, and will allow study of the control of IgA responses and the conditions for IgA complex deposition in the kidney and perhaps in other sites, as occurs in Henoch-Schonlein syndrome. Related questions that can be investigated by the method for quantitating mesangial function will be the possibility of genetic and physiologic influences on the quantitative ability of mesangial transport. This will be studied in various inbred mouse strains, and in rats infused with angiotensin, respectively. The long term goals of this work include further elucidation of the control of the mesangial uptake phenomenon and its role in the development of glomerulonephritis, and of the importance of antibody class and subclass as determinants of the pattern and severity of immune complex disease.